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Part 8: PD Peritonitis |
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China
Correspondence to: C.C. Szeto, Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, PR China. ccszeto{at}cuhk.edu.hk
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ABSTRACT |
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 TOP ABSTRACT CLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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Peritonitis caused by gram-negative bacteria is a serious complication
of peritoneal dialysis. Antibiotic resistance is common, and response to
medical treatment is often poor. In the present article, we review recent
advances in the understanding of the pathogenesis and treatment of this
serious condition.
KEY WORDS: Renal failure; antibiotic resistance; extended-spectrum β-lactamase.
In peritoneal dialysis (PD) patients, peritonitis is a serious complication (1–3) and probably the most important cause of technique failure (2–5). Although gram-positive organisms are the most common bacteriologic cause of PD-related peritonitis (1,6), the incidence of gram-positive infections is falling because of the advances in PD connectology (5,7,8). Gram-negative peritonitis may result from touch contamination, exitsite infection, or possibly a bowel source such as constipation, colitis, or transmural migration, but the cause is often unclear (9–12). Gram-negative organisms now account for 20% – 30% of all PD-related peritonitis (5,13).
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CLINICAL OUTCOMES |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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For example, in a retrospective study, Troidle et al. (11) reviewed 415 episodes of peritonitis that occurred in 375 PD patients between 1993 and 1995. As compared with episodes of gram-positive peritonitis, episodes caused by gram-negative organisms were more likely to require hospital admission (74% versus 24%, p < 0.001) or catheter removal (18% versus 4%, p < 0.001) and to lead to relapse (32% versus 9%, p < 0.05). In the Network 9 Peritonitis Study (10), the risks of catheter loss, hospitalization, and technique failure in 136 episodes of non-Pseudomonas gram-negative peritonitis were significantly worse than in 530 peritonitis episodes caused by gram-positive organisms.
More recently, Choi et al. (14) reviewed 490 episodes of peritonitis that occurred between 1995 and 2002. In that series, 32% of gram-negative and 10% of gram-positive peritonitis episodes required catheter removal (p < 0.0001). In a previous series by our group, gram-negative peritonitis accounted for 43% of the episodes that required catheter removal (4). Although PD could be resumed after catheter re-insertion in about half of the cases, loss of solute clearance or ultrafiltration was common following an episode of severe peritonitis (4).
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SPECIFIC ORGANISMS |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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We previously reported on 104 episodes of Pseudomonas peritonitis (16), which accounted for 13% of all peritonitis in our dialysis unit from 1995 to 1999. The major risk factors were a history of antibiotic therapy within 30 days before onset (66% of cases) and concomitant exit-site infection (45% cases). The overall primary response rate was 61%; the rate of complete cure was 22%. Presence of exit-site infection was associated with a lower primary response rate (47% vs 72%, p < 0.01) and a lower rate of complete cure (11% vs 32%, p < 0.02). The episodes that followed recent antibiotic therapy had a significantly lower rate of complete cure than did the de novo cases (12% vs 43%, p < 0.001). More importantly, among the 24 cases that required catheter removal, the chance of returning to PD was higher when the catheter was removed before day 10 than when it was removed on day 15 (64% vs 50%), although that result was not statistically significant. These findings suggest that, when response to antibiotic therapy is suboptimal, early removal of the catheter is important.
Among all gram-negative organisms, those from the family Enterobacteriaceae, a large heterogeneous group of gram-negative bacteria, are most commonly involved in PD-related peritonitis. We recently reviewed 210 episodes of Enterobacteriaceae peritonitis, which constituted 12% of all peritonitis in our dialysis unit from 1995 to 2004 (17). The most common species was E. coli, which accounted for 111 episodes (53%). The overall primary response rate was 85%; the complete cure rate was 58%. Presence of exit-site infection was associated with a lower rate of complete cure (43% vs 61%, p = 0.034), but not primary response (89% vs 84%, p = 0.3). The episodes that followed recent antibiotic therapy had a marginally lower rate of complete cure than the others did (49% vs 63%, p = 0.06), but the response rate for primary infections was similar. A total of 82 episodes (39%) did not respond to treatment with a single antibiotic despite sensitivity in vitro, and a second antibiotic had to be added. Interestingly, patients treated with two antibiotics had a marginally lower risk of relapse and recurrence than did those treated with one antibiotic (21% vs 36%, p = 0.051).
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EVOLUTION IN EPIDEMIOLOGY |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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We recently reviewed 1787 episodes of PD-related peritonitis in 544 patients treated at our center during 1994 – 2003 (5). From 1994 to 1998, the incidence of peritonitis caused by coagulase-negative staphylococci species declined to 0.06 episodes from 0.21 episodes per year on PD, paralleling a reduction in the use of the spike set for PD during that period. In contrast, the incidence of E. coli and Klebsiella peritonitis remained static during the same period (Figure 1).
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ANTIBIOTIC RESISTANCE |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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At our center, the response rate of gram-negative peritonitis to antibiotic therapy remained static for 10 years (5), but the percentage of cases that needed an alteration of the antibiotic regimen rose from 13.6% in 1994 to 58.7% in 2003 (Figure 2), indicating increasing prevalence of clinical antibiotic resistance. In the series by Zelenitsky et al. (15), the incidence of resistance to ciprofloxacin increased to 47.8% in 1998 from 5.4% in 1992 (p = 0.003).
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It should be noted that an in vitro sensitivity test is often not a reliable guide for clinical practice, especially in the presence of bacterial biofilm adherent to a foreign body. Sepandj et al. (18) compared the minimum inhibitory concentration (MIC) and minimum biofilm-eliminating concentration (MBEC) of 8 isolates of E. coli and another 8 isolates of Pseudomonas species. Antibiotic sensitivities were found to be significantly higher for the planktonic organisms as tested by MIC assay than for the same organisms in their biofilm state as tested by MBEC assay. For example, none of the isolates was resistant to ciprofloxacin by MIC assay, but 10 were resistant by MBEC assay. This observation indicates that clinical judgment concerning therapeutic response is important, and the presence of exit-site infection, which is a surrogate marker of biofilm formation, is a strong indicator of a need for more aggressive therapy.
Extended-spectrum β-lactamase (ESBL)–producing bacteria have been attracting special concern in recent years (19). In general, ESBL confers resistance to ceftazidime, cefotaxime, ceftriaxone, aztreonam, and other oxyimino-β-lactams and is found most often in Klebsiella species and E. coli, although it has also been detected in many other gram-negative pathogens. The prevalence of ESBL is probably underestimated because detection in clinical laboratories is imperfect (19). Traditionally, carbapenems are the ideal agents for therapy (19).
Yip et al. (20) identified 11 episodes of ESBL-producing E. coli peritonitis over a period of 10 years. In their series, use of cephalosporins and gastric acid inhibitors were risk factors for ESBL-producing E. coli peritonitis. Compared with patients having non-ESBL-producing E. coli peritonitis, patients with the ESBL-producing variant more often developed treatment failure (46% vs 13%, p = 0.02) and more often died of sepsis (27% vs 4%, p = 0.02). The peritoneal failure rate was also higher in the group infected with ESBL-producing organisms, although the difference was not statistically significant (18% vs 4%, p = 0.12).
In our center, 7 of 103 isolates of E. coli and Klebsiella species from 1999 to 2003 were positive for ESBL (17). Of those 7 cases, 4 had recently received antibiotic therapy; 3 cases attained complete cure. Although carbapenems are the surest agents for therapy, the variety of β-lactamases that confer resistance to carbapenems is increasing, and overuse of any single class of antibiotic is likely to be followed by selection of pathogens resistant to that agent (19).
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STRATEGIES FOR PREVENTION |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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Bernardini et al. (21) recently reported a multicenter double-blind randomized controlled trial that compared daily gentamicin or mupirocin cream to the catheter exit site. Gentamicin cream applied daily to the catheter exit site reduced P. aeruginosa and other gram-negative catheter infections by more than 50%, and reduced peritonitis by 35%, particularly gram-negative peritonitis. In addition, gentamicin cream was as effective as mupirocin in preventing S. aureus infections. Moreover, gentamicin cream is notably less costly than is mupirocin, to which the incidence of resistance is rising. This study is particularly relevant to countries where gram-negative peritonitis is common.
Once gram-negative peritonitis develops, suboptimal response to antibiotic therapy should lead to consideration of early catheter removal. Although the contemporary guideline recommends that catheter removal be considered by day 4, our recent data suggest that a dialysate cell count exceeding 1000/mm3 on day 3 is a strong predictor of treatment failure and that early catheter removal should then be planned (22).
Relapsed peritonitis is often caused by the persistence of bacterial biofilm on the catheter. Catheter exchange for patients with exit-site infection concurrent with peritonitis is a logical and effective measure to prevent relapse. Lui et al. (23) reviewed 37 patients with refractory Pseudomonas exit-site infection treated with catheter exchange in 1994 and 2003. In all patients, effective antibiotics were continued for 7 days, and PD was resumed 2 weeks after the surgery. None of the patients had recurrent exit-site infection at 4 weeks, and no case of Pseudomonas peritonitis occurred within 1 year. Similarly, in 14 episodes of Pseudomonas peritonitis with concomitant exit-site infection, we performed a catheter exchange procedure after the dialysis effluent cleared (16). In no case did relapse peritonitis occur within 1 year after the catheter exchange. These studies make a strong case for early elective catheter exchange in patients with persistent gram-negative exit-site infection.
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CONCLUSIONS |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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ACKNOWLEDGMENTS |
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REFERENCES |
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TOPABSTRACTCLINICAL OUTCOMESSPECIFIC ORGANISMSEVOLUTION IN EPIDEMIOLOGYANTIBIOTIC RESISTANCESTRATEGIES FOR PREVENTIONCONCLUSIONSREFERENCES |
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This article has been cited by other articles:
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  A Power, N Duncan, and C Goodlad Management of the dialysis patient for the hospital physician Postgrad. Med. J., July 1, 2009; 85(1005): 376 - 381. [Abstract] [Full Text] [PDF]
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 M. Borras ANTIBIOTIC RESISTANCE IN GRAM-NEGATIVE PERITONITIS Perit. Dial. Int., May 1, 2009; 29(3): 274 - 276. [Full Text] [PDF]
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